The Woods Hole Center for Oceans and Human Health (WHCOHH) will comprise a strong and integrated set of research projects using novel in situ sampling technologies and modeling approaches to address harmful algal bloom (HAB) dynamics, and mechanistic studies to expand understanding of HAB toxin effects. The overall objective is to protect the public health through enhanced understanding of how oceanic and environmental processes affect the population dynamics of toxin-producing organisms, and the risks from exposure to their potent neurotoxins, a serious and potentially growing human health threat. The Center will focus on two key HAB taxa: Alexandrium fundyense that produces the saxitoxins responsible for paralytic shellfish poisoning (PSP), and Pseudo-nitzschia spp. that produce domoic acid responsible for amnesic shellfish poisoning (ASP) syndrome. Novel, targeted, efficient, and data-rich sampling approaches developed by the applicants and applied in situ have revealed that critical aspects of A. fundyense dynamics in natural settings differ dramatically from those inferred from laboratory studies, and identified plasticity in these processes. Project 1 will examine the physiological and behavioral factors of toxic Alexandrium species, and how plasticity in these factors may underlie population adaptation in different habitats and different environmental regimes. Project 2 will build on these new and fundamental insights into bloom regulation and develop models to predict impacts of climate variation on population dynamics of HAB threats. Variability in environmental forcing across years and among habitats will provide a proxy for future climate scenarios, revealing responses of HABs in natural ecosystems, a key step toward improving predictive skill for this recurrent public health risk, and quantify future risks. In companion studies we have identified specific cells in the developing brain in the zebrafish model that are targets of HAB toxins. The novel cellular mechanisms include effects of domoic acid on myelination of oligodendrocytes. We will define the consequences of developmental, low-level exposure to HAB toxins, and determine the effects of combined exposure to saxitoxin and domoic acid, and possible silent neurotoxicity, at different life stages, in the zebrafish model. The studies address the scope of toxin effects in the developing central nervous system, potentially linking developmental exposures to adult consequences. Novel linking of oceanic processes to human exposure will help define the human risk due to these novel mechanisms. The Center structure will facilitate integration of the research, and of research projects with education and community engagement activities, including with resource managers and other stakeholders. We also will improve awareness of emerging HAB issues for the public health community and develop new educational materials and interactive activities for K-12 classrooms, and for public outreach. An Administrative Core will create a structure encouraging open discussion of planning, integration, communication and engagement, and in which progress is rigorously evaluated.